The importance and need for continuous metabolites monitoring cannot be overemphasized. Most recent developments for in vivo monitoring devices have focused on the miniaturization and the exploratory use of new functional materials. As most biosensors, however, tend to drift and degrade over time, the development of a simple, dependable, on-demand, in situ (and possibly in vivo) self-calibration/self- diagnosis technique is a key obstacle for convenient, continuous monitoring with minimum intervention. The availability of this "weak link" would greatly improve the reliability and convenience of continuous in situ, in vivo monitoring technology. The objective of this proposal is to develop a novel polymer fluidic microsystem for continuous glucose monitoring, with special emphasis on an unprecedented in situ self-calibration/self-diagnosis capability. This will be accomplished by utilizing the oxygen dependency of a glucose biosensor that employs the glucose oxidase (GOD) enzyme reaction. The proposed microsystem with integrated calibrator, sensor, and debubbler modules establishes the calibrating and diagnostic microenvironment internally, minimizing the need of externally coupled bulky reservoirs and fluidic systems. A new fabrication process for all-polymer fluidic microsystem is developed to integrate unique procedures of low-temperature wafer bonding, post- bonding enzyme immobilization, and post-bonding surface functionalization to minimize biofouling. Innovative on-chip functionalities of the microsystem include: (1) one-point in situ self-calibration (zero-value calibration), (2) increased sensitivity and lower detection limit, and (3) minimization of sensor errors caused by background oxygen fluctuations and electrochemical interferences. The objective of this proposal is to develop a novel glucose sensor system for convenient, continuous monitoring with minimum human intervention. We anticipate this work can lay a foundation for the development of intelligent and autonomous biosensors for continuous metabolites monitoring, especially for diabetes and intensive care unit patients. The impact of this work is very broad since the proposed approach is applicable to many areas of medical diagnosis, bioprocess monitoring, and environmental monitoring. [unreadable] [unreadable] [unreadable]